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High Dose Intravenous Ascorbic Acid in Severe Sepsis

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ClinicalTrials.gov Identifier: NCT02734147
Recruitment Status : Terminated (The trial prematurely terminated due to the loss of funding.)
First Posted : April 12, 2016
Results First Posted : February 16, 2021
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Christiana Care Health Services

Brief Summary:

Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult, and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence continues to rise, making sepsis the most expensive inpatient disease.

  1. Recent research has described the therapeutic benefits associated with ascorbic acid treatment for sepsis.
  2. Researchers objectives are to perform a randomized-controlled clinical trial investigating the ability of ascorbic acid(vitamin C) administration to decrease organ dysfunction in severe sepsis. The widespread occurrence of microvascular dysfunction in sepsis leading to tissue hypoxia, mitochondrial dysfunction, and adenosine triphosphate (ATP) depletion, gives rise to organ failure.
  3. Patients with organ failure and sepsis (severe sepsis) are at a higher risk of death than patients with organ failure alone. Critically ill patients may have an increased requirement for ascorbic acid in sepsis and these patients frequently have levels below normal. Ascorbic acid administration, has been shown to correlate inversely with organ failure (human literature) and directly with survival (animal studies).

4,5 Intravenous ascorbic acid therapy decreases organ failure by providing a protective effect on several microvascular functions including improving capillary blood flow, decreasing microvascular permeability, and improving arteriolar responsiveness to vasoconstrictors. Defining the utility of novel agents to augment researchers care for severe sepsis is an important task as investigators continue the institutional focus on sepsis care.


Condition or disease Intervention/treatment Phase
Sepsis Drug: Ascorbic Acid Other: Normal Saline Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Efficacy of Intravenous Ascorbic Acid in Patients With Severe Sepsis
Study Start Date : April 1, 2016
Actual Primary Completion Date : October 8, 2017
Actual Study Completion Date : November 23, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis Vitamin C

Arm Intervention/treatment
Active Comparator: High dose IV ascorbic acid
Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours.
Drug: Ascorbic Acid
Placebo Comparator: Placebo
The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours.
Other: Normal Saline



Primary Outcome Measures :
  1. Change in Modified SOFA Score [ Time Frame: Baseline and 72 hours ]
    Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater degree of dysfunction.


Secondary Outcome Measures :
  1. Modified SOFA Score [ Time Frame: at 72 Hours ]
    Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater dysfunction.

  2. Ascorbic Acid Concentration at 32 Hours [ Time Frame: 32 Hours ]
    Ascorbic Acid Concentration Normal Ascorbic Acid Range 0.4-2.0 mg/dL

  3. ICU Length of Stay [ Time Frame: Length of ICU stay up to 200 hours ]
    ICU Length of Stay in Hours

  4. Hospital Length of Stay [ Time Frame: From ICU admission through ICU discharge, up to 2 weeks ]
    From admission until discharge from ICU in days

  5. Change in PIRO Score [ Time Frame: Baseline and 72 hours ]
    PIRO consists of 4 assessments, Predisposition (scored 0-9), Infection (scored 0-4), Response (scored 0-6), and Organ Failure (scored 0-14) (PIRO). The total PIRO score is the sum of all subscores and ranges from 0-33 with higher scores indicating worse health.

  6. Percentage of Participants Who Died [ Time Frame: From initial hospital admission through discharge, up to 2 weeks. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with:

  1. A suspected or confirmed infection with an order for intravenous antibiotics or antivirals
  2. The presence of acute sepsis-induced organ dysfunction

Definition of organ dysfunction:

  1. Arterial hypoxemia [PaO2 /FiO2 < 300]
  2. Hypotension [systolic blood pressure (SBP) < 90 mmHg or SBP decrease > 40 mmHg]
  3. Lactic acidosis [lactate > 2.5 mmol/L]
  4. Acute kidney injury [creatinine >2.0 or urine output < 0.5 ml/kg/hr for >2 hours despite fluid resuscitation]
  5. Thrombocytopenia [platelet count < 100,000]
  6. Acute coagulopathy [international normalized ratio (INR) > 1.5]
  7. Hepatic failure [bilirubin > 2 mg/dL].
  8. Predisposition, Infection, Response, and Organ Failure (PIRO) score ≥ 10

Exclusion Criteria:

  1. Age < 18 years
  2. Pregnancy or breastfeeding
  3. Requirement for immediate surgery within the treatment protocol timeframe
  4. Inability to obtain written informed consent from subject or surrogate
  5. Patient to receive comfort measures only

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734147


Locations
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United States, Delaware
Chrisitana Care Health System-Christiana Hospital
Newark, Delaware, United States, 19718
Sponsors and Collaborators
Christiana Care Health Services
Investigators
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Principal Investigator: Ryan Arnold, MD Christiana Care Health Services
Principal Investigator: Jamie Rosini, PharmD Christiana Care Health Services
  Study Documents (Full-Text)

Documents provided by Christiana Care Health Services:
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Responsible Party: Christiana Care Health Services
ClinicalTrials.gov Identifier: NCT02734147    
Other Study ID Numbers: 603204
First Posted: April 12, 2016    Key Record Dates
Results First Posted: February 16, 2021
Last Update Posted: February 16, 2021
Last Verified: January 2021
Additional relevant MeSH terms:
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Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Ascorbic Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Nutrients
Growth Substances